Mathematical model of acetylcholine kinetics in neuroeffector junctions

Franklin Dexter; Yoram Rudy; Gerald M Saidel

doi:10.1152/ajpheart.1994.266.1.H298

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Mathematical model of acetylcholine kinetics in neuroeffector junctions

Journal article

Peer reviewed

Mathematical model of acetylcholine kinetics in neuroeffector junctions

Franklin Dexter, Yoram Rudy and Gerald M Saidel

The American journal of physiology, Vol.266(1 Pt 2), pp.H298-H309

01/1994

DOI: 10.1152/ajpheart.1994.266.1.H298

PMID: 8304512

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Abstract

Acetylcholine (ACh) kinetics in neuroeffector junctions (NEJ) of the sinus node plays a key role in vagal control of heart rate. Prior studies have shown that the concentration of ACh ([ACh]) in NEJ appears to follow first-order linear kinetics. To find out the reason why, we examine mathematically diffusion, degradation, and receptor binding of ACh in NEJ. We identify seven conditions that potentially influence ACh kinetics. Because these conditions are satisfied for NEJ in the sinus node, 1) the nonlinearity of ACh binding to muscarinic receptors has little effect on [ACh]; 2) [ACh] does not depend on the distribution of acetylcholinesterase between the interstitial space and the pacemaker cells; 3) the interval from trough to subsequent peak [ACh] at the pacemaker cells is negligible; 4) the mean [ACh] at the pacemaker cells is proportional to the frequency of vagal activity multiplied by the amount of ACh released per vagal stimulus and divided by the rate coefficient of ACh degradation; and 5) [ACh] at pacemaker cells nearly follows first-order linear kinetics but does not at other sites in the NEJ. We conclude that earlier studies showed that [ACh] follows first-order linear kinetics, because they predicted [ACh] only at pacemaker cells. ACh kinetics at other sites in the NEJ, such as at nerve endings, is different.

Models, Cardiovascular

Humans

Sinoatrial Node - cytology

Receptors, Muscarinic - metabolism

Acetylcholine - metabolism

Tissue Distribution

Vagus Nerve - physiology

Animals

Time Factors

Sinoatrial Node - metabolism

Kinetics

Models, Neurological

Neuroeffector Junction - metabolism

Details

Title: Subtitle: Mathematical model of acetylcholine kinetics in neuroeffector junctions
Creators: Franklin Dexter - Department of Anesthesia, University of Iowa Hospitals, Iowa City 52242
Yoram Rudy
Gerald M Saidel
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.266(1 Pt 2), pp.H298-H309
DOI: 10.1152/ajpheart.1994.266.1.H298
PMID: 8304512
NLM abbreviation: Am J Physiol
ISSN: 0002-9513
eISSN: 2163-5773
Publisher: United States
Grant note: HL-10951 / NHLBI NIH HHS HL-49054 / NHLBI NIH HHS
Language: English
Date published: 01/1994
Academic Unit: Health Management and Policy; Anesthesia
Record Identifier: 9983805901802771

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